Maeda Yoshihisa, Hirano Katsuya, Hirano Mayumi, Kikkawa Yuichiro, Kameda Katsuharu, Sasaki Tomio, Kanaide Hideo
Division of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Stroke. 2009 Feb;40(2):591-6. doi: 10.1161/STROKEAHA.108.530196. Epub 2008 Dec 18.
The level of platelet-derived growth factor (PDGF) in cerebrospinal fluid is elevated in subarachnoid hemorrhage (SAH). Therefore, the contractile effect of PDGF on the basilar artery was examined in SAH.
A rabbit double-hemorrhage SAH model was used. In the medial layers of the control basilar artery, PDGF had no effect on contraction up to 1 nmol/L, whereas 3 nmol/L PDGF induced slight contraction. In SAH, PDGF induced an enhanced contraction with an increase in Ca(2+) at 1 nmol/L and higher concentrations. The levels of Ca(2+) and tension induced by 1 nmol/L PDGF in SAH were 17% and 20%, respectively, of those obtained with 118 mmol/L K(+) depolarization. The PDGF-induced elevation of Ca(2+) and contraction seen in SAH were abolished in the absence of extracellular Ca(2+). In alpha-toxin-permeabilized strips of SAH animals, PDGF induced no further development of tension during contraction induced by 300 nmol/L Ca(2+), suggesting no direct effect on myofilament Ca(2+) sensitivity. Genistein at 10 micromol/L completely inhibited the tension induced by 1 nmol/L PDGF. The level of myosin light-chain phosphorylation was significantly increased by 1 nmol/L PDGF.
These results show that the contractile response to PDGF of the basilar artery was enhanced in SAH. The PDGF-induced contraction depended mostly on tyrosine phosphorylation and Ca(2+)-dependent myosin light-chain phosphorylation. The enhancement of the responsiveness to PDGF may therefore contribute to the development of cerebral vasospasm after SAH.
蛛网膜下腔出血（SAH）时脑脊液中血小板衍生生长因子（PDGF）水平升高。因此，研究了SAH时PDGF对基底动脉的收缩作用。
采用兔双次出血SAH模型。在对照基底动脉的中层，高达1 nmol/L的PDGF对收缩无影响，而3 nmol/L的PDGF诱导轻微收缩。在SAH中，1 nmol/L及更高浓度的PDGF诱导增强的收缩，并伴有细胞内钙离子浓度（Ca(2+)）升高。SAH中1 nmol/L PDGF诱导的Ca(2+)水平和张力分别为118 mmol/L K(+)去极化时的17%和20%。在无细胞外钙离子的情况下，SAH中PDGF诱导的Ca(2+)升高和收缩消失。在SAH动物的α-毒素通透肌条中，300 nmol/L钙离子诱导收缩期间，PDGF未诱导张力进一步增加，提示对肌丝钙离子敏感性无直接影响。10 μmol/L的染料木黄酮完全抑制1 nmol/L PDGF诱导的张力。1 nmol/L PDGF显著增加肌球蛋白轻链磷酸化水平。
这些结果表明，SAH时基底动脉对PDGF的收缩反应增强。PDGF诱导的收缩主要依赖酪氨酸磷酸化和钙离子依赖性肌球蛋白轻链磷酸化。因此，对PDGF反应性的增强可能有助于SAH后脑血管痉挛的发生。
